Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.
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Acknowledgements
The authors would like to thank the TSC families involved in this study, and their attending physicians, for their participation and cooperation, and C Withagen-Hermans for performing the loss of heterozygosity study. Financial support was provided by the Tuberous Sclerosis Alliance (USA), Noortman b.v., Maastricht and the Nationaal Epilepsie Fonds (Netherlands).
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Goedbloed, M., Nellist, M., Verhaaf, B. et al. Analysis of TSC2 stop codon variants found in tuberous sclerosis patients. Eur J Hum Genet 9, 823–828 (2001). https://doi.org/10.1038/sj.ejhg.5200728
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DOI: https://doi.org/10.1038/sj.ejhg.5200728
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